Tramadol

PEP Topic

Chronic Pain

Description

Tramadol is an analgesic used to relieve moderate to moderately severe pain. Tramadol, which is in a class of medications called opiate agonists, is available as a tablet and an extended-release (long-acting) tablet to take by mouth.

Type of Resource/Evidence-Based Process:

PROCESS OF DEVELOPMENT: An interdisciplinary panel of experts in cancer pain management prepared these guidelines. When unavailable, recommendations were not made or were made on the recommendation of experts in that area.

Results Provided in the Reference:

Guidelines & Recommendations:

Make patient and family caregiver education about pain management a part of the treatment plan, and encourage patient and family caregivers to participate actively in pain management.

Collaborate with patients and family caregivers, taking costs and availability of treatment options into account when selecting pain management strategies. (Panel consensus)

Assessment

Perform a comprehensive pain assessment of all patients with cancer at each outpatient visit or hospital admission and use each patient’s self-report as the foundation for the assessment.

Include in the comprehensive pain assessment a detailed history to determine the presence of persistent and breakthrough pain and its effects on function; a psychosocial assessment; a physical examination; and a diagnostic evaluation of signs and symptoms associated with common cancer pain presentations and syndromes.

Cancer Pain Management

Develop a systematic approach to cancer pain management and teach patients and family caregivers how to use effective strategies to achieve optimal pain control.

Begin a bowel regimen to prevent constipation when the patient is started on an opioid analgesic.

Administer a long-acting opioid on an around-the-clock basis, along with an immediate-release opioid to be used on an as-needed basis, for breakthrough pain once the patient’s pain intensity and dose are stabilized.

Do not use meperidine in the management of chronic cancer pain.

Adjust opioid doses for each patient to achieve pain relief with an acceptable level of side effects.

Avoid intramuscular administration because it is painful and absorption is unreliable.

Use optimally titrated doses of opioids and maximal safe and tolerable doses of coanalgesics through other routes of administration before considering spinal analgesics. (Panel consensus)

Monitor for and prophylactically treat opioid-induced side effects.

Clarify myths and misconceptions about pain management, and reassure patients and family caregivers that cancer pain can be relieved and that addiction and tolerance are not problems associated with effective cancer pain management.

Use cognitive and behavioral strategies as part of a multimodal approach to cancer pain management, not as a replacement for analgesic medications.

Implement a formal process to evaluate and improve the quality of cancer pain management across all stages of the disease process and across all practice settings.

Evaluate the quality of cancer pain management at points of transition in the provision of services (e.g., from the hospital to the home) to ensure that optimal pain management is achieved and maintained.

Research Evidence Summaries

Leppert, W., & Majkowicz, M. (2010). The impact of tramadol and dihydrocodeine treatment on quality of life of patients with cancer pain. International Journal of Clinical Practice, 64(12), 1681–1687.

Study Purpose:

To compare the impact of tramadol to that of dihydrocodone (DHC) treatment on the quality of life (QoL) and performance status (PS) of patients with cancer pain

Intervention Characteristics/Basic Study Process:

Patients received treatment with either tramadol or DHC controlled-release tablets for seven days. Then drugs were switched and administered for another seven days. QoL and PS were measured at baseline, at the 7th day, and on the 14th day of therapy.

Sample Characteristics:

The sample was composed of 30 patients who completed the study; 40 patients were recruited for the study.

Measurement Instruments/Methods:

European Organization for Results and Treatment of Cancer quality of life questionnaire (EORTC QLQ C-30), an instrument developed for use in international clinical trials in oncology, which includes scales measuring physical, role (work), cognitive, emotional, and social functioning and global QoL as well as symptom-measuring scales relating to fatigue, nausea and vomiting, pain, dyspnea, sleep, appetite, constipation, diarrhea, and finances.

Eastern Cooperative Oncology Group (ECOG) scale and Karnofsky Performance Status Score, to measure performance status. (Authors did not describe performance measurement in detail. Performance status is the dependent variable; the independent variables are drug influence, treatment time effect, and interaction of drug and treatment time.)

Results:

More patients in the tramadol group (12 patients) used rescue analgesics than did patients in the DHC group (8).

ANOVA for functional scales of EORTC QLQ-C30 showed higher scores of emotional functioning in the tramadol group and higher global QoL and better cognitive functioning in the DHC group. Authors noted a trend toward better physical functioning in the DHC group (p = 0.063 for treatment time, p = 0.09 for interaction of drug and treatment time).

Conclusions:

DHC treatment was associated with better global QoL, cognitive functioning, analgesia, and appetite and with less fatigue, sleep disturbances, nausea, and vomiting. Tramadol therapy was associated with better emotional functioning, less constipation, and fewer financial problems. Performance status deteriorated in both groups.

Limitations:

The study had a small sample, with fewer than 100 patients.

The study had a risk of bias due to no control group, no blinding, and no washout period before the drug switch.

The treatment period for each analgesic (seven days for each) was very brief.

Nursing Implications:

Findings suggest that the decision between tramadol and DHC should be based on each patient's status and symptoms of concern. To date, no other studies have compared tramadol to DHC in patients with cancer-elated pain. Further research would be beneficial.

Study Purpose:

To facilitate dose escalation of strong opioids by using an opioid-tramadol combination

Intervention Characteristics/Basic Study Process:

Of 70 patients, 35 were treated conventionally, with increasing transdermal fentanyl (group F). The other 35 patients received oral tramadol added to their fentanyl before each increment of their transdermal opioid (group T). Patients started fentanyl therapy by taking 25, 50, 75, or 100 mcg/hour, the amount based on equianalgesic dosing. Maximum tramadol dose was 400 mg/day. Rectal tramadol was not used.

Sample Characteristics:

The sample was composed of 70 patients with intractable cancer pain whose visual analog pain score was greater than 3.

All patients were receiving palliative care and not in the active treatment phase of disease.

Setting:

The study was conducted in Italy.

Study Design:

Randomized open-label, prospectively evaluated study

Measurement Instruments/Methods:

Authors used a visual analog scale (VAS) to measure pain.

Results:

In group F, 33 patients completed the study; in group T, 34 patients completed the study.

Pain was equal in both groups; VAS scores did not differ. However, pain control in the tramadol group was achieved at slower escalation of fentanyl dose. The combination of a strong opioid with a weak opioid, to treat severe cancer pain, allowed a more gradual increase of analgesic delivery. Therefore, the combination minimized periods of overdosing and underdosing.

Application time for patches was significantly higher in group T. In group T, no patient's fentanyl patch dose changed before the patient reached the maximum tramadol dose of 400 mg per day.

Regarding adequacy of treatment, patients’, relatives’, and physicians’ judgments did not differ.

Conclusions:

The combination of a strong opioid and a weak opioid, to treat severe cancer pain, allowed a more gradual increase of analgesic delivery. Therefore, the combination treatment minimized periods of overdosing and underdosing. Combination treatment as specified is a useful alternative, especially when disease and pain progress quickly.

Limitations:

Severe nausea and vomiting occurred in six patients in group T and three in group F, possibly due to a synergistic effect between fentanyl and tramadol. This study was insufficiently powered to show statistically significant differences relating to uncommon or serious side effects.

Nursing Implications:

The greater number of fentanyl dose changes associated with higher fentanyl consumption in group F may support the hypothesis that tolerance is a pharmacologic effect, rather than a result of the rapid progression of disease. Additional study of the synergistic effect of tramadol and fentanyl, with respect to severe nausea and vomiting, is needed.

Study Purpose:

To compare the analgesic activity and tolerability of orally administered and rectally administered tramadol

Intervention Characteristics/Basic Study Process:

In this crossover trial, 30 patients started with orally administered tramadol and switched to rectally administered tramadol and 30 patients started with rectally administered tramadol and switched to orally administered tramadol.

Sample Characteristics:

The sample was composed of 60 patients, with moderate to severe cancer pain (a score of 4 or greater on a 0–10 scale) of nonneurpoathic origin, who were no longer responsive to nonopioid drugs.

Of all participants, 36 were female and 24 were male. Forty-four patients completed both periods.

Results:

Fifteen patients dropped out because of adverse effects; one patient refused treatment.

Most physicians and patients favored oral administration.Three patients eliminated suppository within one hour of rectal administration.

Authors found no differences in the adverse effect profiles of orally and rectally administered tramadol.

Conclusions:

Rectal administration of tramadol appears to be a reliable, noninvasive alternative method of pain control for patients who are no longer responsive to nonopioid analgesics and who are unable to take oral tramadol. Rectal administration of tramadol appears to be as safe and effective as oral administration.

Limitations:

The study had a high dropout rate, with 25% of patients dropping out.

Nursing Implications:

Rectal irritation has occurred with rectal administration of tramadol. If the patient is neutropenic or thrombocytopenic, rectal administration may be contraindicated. Patients with diarrhea will have difficulty maintaining and absorbing tramadol. Patients with lack of rectal tone will not be able to keep the suppository in the rectal vault.

Study Purpose:

To compare the efficacy of hydrocodone-acetaminophen with that of tramadol in the management of cancer pain; to compare the tolerability of hydrocodone-acetaminophen and tramadol used to relieve cancer pain

Intervention Characteristics/Basic Study Process:

Patients were assigned to receive either hydrocodone-acetaminophen (25 mg hydrocodone, 2,500 acetaminophen) or tramadol (200 mg) for 21 days. Patients rated pain intensity at the beginning of the study, two days after the beginning of the study, and once weekly for three weeks. Patients were to note all adverse events.

Sample Characteristics:

The sample was composed of 118 patients.

In the hydrocodone-acetaminophen group, mean patient age was 62 years. In the tramadol group, mean patient age was 57.1 years.

In the hydrocodone-acetaminophen group, 35.5% were female and 64.5% were male. In the tramadol group, 62.5% were female and 37.5% were male.

In the entire sample, 13.5% of patients had pain due to gastric cancer; 12%, to breast cancer; 13.5%, to prostate cancer; and 89%, to lung cancer.

Authors noted no significant differences between groups in regard to dry mouth or constipation.

Conclusions:

In this study, tramadol and hydrocodone-acetaminophen were equally efficacious in relieving cancer pain. Patients taking hydrocodone-acetaminophen experienced fewer side effects than did patients who took tramadol.

Limitations:

All analgesics, except medications for neuropathic pain, were discontinued. Note that the group that took tramadol contained significantly more women than did the group that took hydrocodone-acetaminophen. This difference may relate to the differing side-effect profiles.

Nursing Implications:

This study showed that hydrocodone-acetaminophen and tramadol were equally effective at treating cancer pain; however, tramadol was associated with more adverse effects. Nurses should keep this in mind and provide patients with anticipatory guidance as appropriate.